Purpose: Mutations in RAD51D are associated with a predisposition to primary ovarian, fallopian tube, and peritoneal carcinoma. Our study aims to characterize a RAD51D missense variant in a hereditary ovarian cancer family.
Methods: The effects of the RAD51D c.82G>A (p.Val28Met) variant on mRNA splicing were evaluated and characterized using RT-PCR, cloning and DNA sequencing.
Results: This variant completely disrupts normal splicing and results in the loss of 3'end of 5'UTR and the entire exon 1 (c.-86_c.82), which presumably leads to loss of the RAD51D protein. The RAD51D c.82G>A (p.Val28Met) variant is clinically significant and classified as likely pathogenic.
Conclusions: Our results indicate that the RAD51D c.82G>A (p.Val28Met) variant contributes to cancer predisposition through disruption of normal mRNA splicing. The identification of this variant in an individual affected with high-grade serous fallopian tube cancer suggests that the RAD51D variant may contribute to predisposition to the ovarian cancer in this family.
Keywords: Missense variant; Ovarian cancer; RAD51D; Splicing.